Effect of Excipients on the Performance of Spray-dried Amorphous Solid Dispersion (ASD) in Tablets

Abstract

Amorphous solid dispersions (ASD) are a proven method of improving the solubility and bioavailability of poorly soluble drugs. Immediate-release tablets are frequently used as the final dosage form for ASDs. The selection of polymers and excipients is critical for the manufacturability and bioavailability of ASD tablets. ASDs were prepared by spray drying; ASD tablets were then generated using a compaction simulator. We first studied the impact of polymer types and drug-polymer ratios on bulk powder properties, morphologies, and compaction behaviors of ASDs. Itraconazole (ITZ) and indomethacin (IND) were used as model drugs, and two polymers were used: hydroxypropyl methylcellulose acetate succinate (HPMCAS) and polyvinylpyrrolidone (PVP). The results indicated that the tabletability increased with decreasing drug loadings, except for ITZ-PVP ASDs. Multivariate analysis revealed that particle surface area was the most significant factor influencing the tensile strength of ASD tablets. Secondly, the contact angle and surface free energy of ITZ ASD tablets containing different HPMCAS grades and drug loadings were evaluated using a Drop Shape Analyzer. A larger contact angle was correlated with a higher dissolution rate, suggesting that contact angle could be a high throughput tool for screening ASDs formulations. Lastly, we investigated the influence of fillers such as microcrystalline cellulose, lactose, mannitol, and starch on drug release and stability of ITZ-HPMCAS ASDs. We discovered that the dissolution performance and physical stability of tablets were influenced by the choice of filler. The results and inferences drawn from this research will provide valuable insights into ASD formulation development downstream tablet production.